Clinical Trial Simulation in Diabetic Retinopathy: Insights from Patients and Site Staff

Introduction: High patient burdens from diabetic retinopathy (DR)-associated vision loss and intravitreal therapy (IVT) support patient experience inclusion in DR trial designs. This trial simulation characterized patient and site staff opinions to improve future nonproliferative DR (NPDR) trial designs. Methods: Between March 27 and May 31, 2023, survey data were collected from trial simulation participants. After a preread and trial design animation, study features were simulated followed by a 75-90-min web-assisted telephone interview. Patients with NPDR and trial site staff from the United States, United Kingdom, and Germany were included. The likelihood of patient participation and the challenges faced by site staff in conducting the simulated clinical trial at their study site were assessed using a 1-7 scale. Outcomes were evaluated via thematic analysis and descriptive statistics. Results: Twenty-two patients aged 36-55 years and mostly female (59.1%), and 16 site staff were interviewed. Mean NPDR duration was 9.3 years; most patients (81.8%) had never participated in a clinical trial. Although eligibility criteria resembled other trials, site staff indicated that restrictive exclusion criteria of the trial simulation could limit recruitment and that endpoints did not match patients' goals, which mainly focused on saving vision. The proposed 4-5-h on-site visits and 72-week trial length were considered "too long" by 45.5% and 50.0% of patients, respectively. For the 1:2 sham or active treatment allocation ratio, responses were 40.9% neutral, 36.4% positive, and 22.7% negative. Some patients misunderstood that sham injections imitate actual injections, expressing concerns about adverse events. Patients reported IVT-related anxieties, particularly IVT-inexperienced patients. Mean patient trial participation interest score was 4.9/7; 62.5% of site staff were interested in conducting the trial. Some proposed adaptations were implemented in the trial protocol (e.g., offering patient/caregiver transportation). Conclusions: Insights gained from respondent feedback in this simulation may inform future DR clinical trial design, potentially enhancing recruitment rates and patient experience.